Pharmacological uncoupling of activation induced increases in CBF and CMRO2

Neurovascular coupling provides the basis for many functional neuroimaging techniques. Nitric oxide (NO), adenosine, cyclooxygenase, CYP450 epoxygenase, and potassium are involved in dilating arterioles during neuronal activation. We combined inhibition of NO synthase, cyclooxygenase, adenosine receptors, CYP450 epoxygenase, and inward rectifier potassium (Kir) channels to test whether these pathways could explain the blood flow response to neuronal activation. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO₂) of the somatosensory cortex were measured during forepaw stimulation in 24 rats using a laser Doppler/spectroscopy probe through a cranial window. Combined inhibition reduced CBF responses by two-thirds, somatosensory evoked potentials and activation-induced CMRO₂ increases remained unchanged, and deoxy-hemoglobin (deoxy-Hb) response was abrogated. This shows that in the rat somatosensory cortex, one-third of the physiological blood flow increase is sufficient to prevent microcirculatory increase of deoxy-Hb concentration during neuronal activity. The large physiological CBF response is not necessary to support small changes in CMRO₂. We speculate that the CBF response safeguards substrate delivery during functional activation with a considerable ‘safety factor''. Reduction of the CBF response in pathological states may abolish the BOLD–fMRI signal, without affecting underlying neuronal activity.     

Patients taking medications for bipolar disorder are more prone to metabolic syndrome than Korea's general population

Despite growing concerns about the co-morbidity of metabolic syndrome (MetS) and bipolar disorder, few studies have been conducted on this topic in Asian populations. This study examined Korean patients with bipolar disorder to assess its co-morbidity with MetS and to compare the prevalence of MetS in patients with medication for bipolar disorder with that of healthy patients. We used cross-sectional data from the medical records of patients with bipolar disorder who presented to the psychiatric clinic in Seoul National University Hospital between June 2007 and June 2008. The control group, matched for age and gender, was randomly drawn from visitors to the Health Promotion Center at the same hospital during the same period. We compared the prevalence of MetS between these two groups with independent sample t-tests and chi-squared tests. We also calculated the indirectly standardized prevalence ratio (ISPR) with a standardization that used the Fourth Korean National Health and Nutrition Examination Survey (KNHNES, 2007). The prevalence of MetS in patients who took medication for bipolar disorder (N = 152) was 27.0%, 25.0% and 25.7%, based on the definitions of the American Heart Association and the National Heart, Lung and Blood Institute's adaptation of the Adult Treatment Panel III (AHA), the National Cholesterol Education Program for Adult Treatment Panel III (ATPIII) and the International Diabetes Federation (IDF), respectively. The present study determined that the prevalence of MetS was significantly higher in patients with bipolar disorder than in the control group; the odds ratios (OR) (95% CI) were 2.44 (1.35–4.40), 2.48 (1.34–4.59) and 2.57 (1.40–4.74), based on the definition of the AHA, ATPIII and IDF, respectively. The ISPR (95% CI) was 1.48 (1.02–1.93), 1.54 (1.05–2.03) and 1.98 (1.36–2.60), respectively. Patients with medications for bipolar disorder showed a significantly higher prevalence of increased waist circumference, elevated triglycerides, and reduced HDL-cholesterol than the control group. The prevalence of MetS in patients taking medication for bipolar disorder was higher than that in the general population. Obesity and dyslipidemia were particularly prevalent in patients with bipolar disorder.     

Metabolic syndrome and cerebral vasomotor reactivity

Background and purpose: Metabolic syndrome has been proposed as a risk factor for stroke and transient ischaemic attack. One pathophysiological mechanism could be impairment of endothelial function. Thus, we hypothesized that cerebral vasomotor reactivity would be decreased in patients with metabolic syndrome, compared to patients without metabolic syndrome. Methods: In this retrospective analysis, 83 consecutive patients (aged 59.19 ± 15.98; 33 women) underwent Doppler examination for carotid artery disease including bi‐hemispherical vasomotor reactivity assessment using transcranial Doppler monitoring. Vasomotor reactivity data were analyzed from the hemisphere with no or low‐grade carotid stenosis (<40%). Cerebral vasomotor reactivity was calculated as percent increase in mean flow velocity per mmHg pCO₂ during 2 min of 5% CO₂ inhalation delivered by anesthesia mask (normal if ≥2%/mmHg). Univariate and multivariable linear regression models were used to determine factors, including metabolic syndrome, that were independently associated with pathologic vasomotor reactivity. Results: After adjusting for the presence of contralateral carotid stenosis and ipsilateral stroke in the multivariable model, metabolic syndrome was independently associated with lower vasomotor reactivity values (2.27 ± 1.24% vs. 2.68 ± 1.37; ß = ?0.258, P = 0.033). In this model, there was no association of cerebral vasomotor reactivity with age, gender, race, cardiac disease, current statin therapy, or small vessel disease. Conclusions: Our findings suggest that impaired cerebral vasomotor reactivity may be a mediator of stroke in patients with metabolic syndrome, a syndrome affecting a significant and growing proportion of the population. A prospective longitudinal study is warranted to study the cerebral haemodynamic effect of metabolic syndrome.     

Simultaneous combined liver and kidney transplantation: a single center experience

Chava SP, Singh B, Stangou A, Battula N, Bowles M, O’Grady J, Rela M, Heaton ND. Simultaneous combined liver and kidney transplantation: a single center experience.
Clin Transplant 2010: 24: E62–E68. © 2010 John Wiley & Sons A/S. Abstract Renal dysfunction is common in patients awaiting liver transplantation (LT) and affects outcome following LT. Combined liver and kidney transplantation (CLKT) has been proposed as effective treatment for patients with chronic diseases of both organs, some with hepatorenal syndrome and for liver‐based metabolic diseases affecting kidney. This study is undertaken to analyze results of CLKT at a single center. Of 2690 LTs performed between 1992 and 2007, there were 39 CLKTs; most common indications were metabolic, cirrhosis and polycystic disease. With follow‐up of up to 170 months, 11 died (overall survival 71.8%); one‐, five‐, and 10‐yr patient and liver graft survival is 77%, 73.7%, and 73.7%, respectively, and kidney graft survival is 77%, 70%, and 70%, respectively. Survival among metabolic group (78.6%) appeared to be better than non‐metabolic group (68%); however, this difference was not significant (p = 0.39). Fifteen surviving patients (53.6%) have mild/moderate renal impairment (creatinine ≥125 μmol/L). None has severe renal failure (serum creatinine ≥250 μmol/L) or end‐stage renal disease requiring hemodialysis. CLKT has good results in selected groups of patients. It provides protection to kidney allograft in liver‐based metabolic diseases affecting kidney. The rate of acute rejection episodes of kidney is low. Significant proportion develops long‐term mild/moderate renal dysfunction. Careful attention to immunosuppression to minimize nephrotoxicity may help.     

Fatty Acid Synthase Inhibitors from Plants and Their Potential Application in the Prevention of Metabolic Syndrome

Fatty acid synthase (FAS) attracts more and more attention recently as a potential target for metabolic syndrome,such as cancer, obesity, diabetes and cerebrovascular disease. FAS inhibitors are widely existed in plants, consisting of diversiform compounds. These inhibitors exist not only in herbs also in many plant foods, such as teas, allium vegetables and some fruits. These effective components include gallated catechins, theaflavins,flavonoids, condensed and hydrolysable tannins, thioethers,pentacyclic triterpenes, stilbene derivatives, etc, and they target at the different domains of FAS, showing different inhibitory mechanisms. Interestingly, these FAS inhibitor-contained herbs and plant foods and their effective components are commonly related to the prevention of metabolic syndromes including fatreducing and depression of cancer. From biochemical angle,FAS can control the balance between energy provision and fat production. Some studies have shown that the effects of those effective components in plants on metabolic syndromes are mediated by inhibiting FAS. This suggests that FAS plays a critical role in the regulation of energy metabolism, and the FAS inhibitors from plants have significant potential application value in the treatment and prevention of metabolic syndromes.     

补阳还五汤干预代谢综合征血管性血友病因子的研究

目的:观察补阳还五汤干预代谢综合征(MetS)模型血管性血友病因子(vWF)的作用和初步探讨其机制。方法:52只雄性Wistar大鼠随机分为正常、模型对照、补阳还五汤、补阳还五汤去黄芪方4组,采用高糖脂餐加链脲佐菌素建立MetS模型,补阳还五汤组按7.02 g.kg-1 ig,1次/d给药,补阳还五汤去黄芪方组按1.07 g.kg-1 ig,1次/d给药,造模和给药同时进行并持续8周,观察补阳还五汤及其去黄芪方对空腹血糖(FBG),血清胰岛素(Ins),稳态模型评价胰岛素抵抗(HOMA-IR)和血清vWF水平的影响。结果:模型组Ins,HOMA-IR,vWF较正常组明显升高(P<0.05);与模型组比较,补阳还五汤组的Ins,HOMA-IR,vWF明显降低(P<0.05);补阳还五汤去黄芪方组Ins,HOMA-IR与模型组比较无统计学差异,FBG明显升高(P<0.01),vWF明显降低(P<0.05)。结论:补阳还五汤能够改善MetS模型的胰岛素抵抗和降低vWF水平;方中黄芪是改善胰岛素抵抗的有效成分,6味活血药是降低vWF的有效成分。     

重视内分泌代谢病的脑卒中诊断与治疗

内分泌代谢病的脑卒中系由内分泌或代谢性疾病所引起或合并的脑血管或颅内其他血管病变,其中有些卒中目前少有文献论及,也易导致临床误诊和漏诊。为提高对本病的认识及医疗质量,现将其临床诊治特点进行探讨。